Free and sulfoconjugated catecholamine responses to hypoxia in fetal sheep

Plasma catecholamines circulate either in conjugated or unconjugated forms. In adult humans, sulfoconjugated catecholamines predominate; however, there is considerable variation between species. In a variety of pathophysiological states catecholamine conjugation is believed to represent an important mechanism of inactivation of high circulating catecholamine levels. To date, there have been few data in developing animals or humans on catecholamine sulfoconjugation. We studied the differences in free and sulfoconjugated catecholamines in full term (141 +/- 1 days) and preterm (123 +/- 1 days) chronically catheterized fetal sheep and determined the changes in free and sulfoconjugated catecholamines in response to hypoxia. The results demonstrate that term and preterm animals have a comparable percentage of basal circulating sulfoconjugated catecholamines (free-to-total ratio 50-60%). In response to hypoxia, both free and sulfoconjugated catecholamines were promptly elevated with significant increases in each by 5 min of hypoxia. This was true for both term and pretern animals. The proportion of free and total catecholamines remained relatively constant during hypoxia despite a 5- to 10-fold increase in circulating levels of each. These data demonstrate that fetal sheep, as early as 80% gestation, have a well developed mechanism for sulfoconjugation and subsequent inactivation of the high circulating levels of catecholamines seen during fetal and newborn life.